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Abstract First isolated in 1981, Mycoplasma genitalium is now well recognized as a frequent cause of urethritis and several other urogenital syndromes in both men and women. The cytoadhesins P110 (MgpC) and P140 (MgpB), located in the terminal organelle of the bacterium, mediate the establishment and persistence of M. genitalium infection in the reproductive tract tissues. This adhesion complex exposes a large extracellular domain, mediating bacterial adhesion to the anogenital tissue. The antigenic variation promoted by reciprocal recombination contribute to the efficient colonization of the urogenital environment and the immune evasion strategy of the bacterium. Although M. genitalium was traditionally detected in ano-genital samples, sexual transmission was not postulated until the early 2000s. Now, it is well accepted that M. genitalium can lead to a sexually transmitted infection. While vaginal sex may constitute the primary transmission route in terms of risk, anal intercourse in men who have sex with men is likely the most common cause of spread. Acknowledging the exquisite adaptation of the bacterium to diverse ecological niches in the human body, the unique features of the proteins P110 and P140 may influence transmission, dissemination and disease. Cytadhesins P110 and P140 are key for the pathogenesis and transmission of Mycoplasma genitalium infection

Mycoplasma pneumoniae is a bacterial human pathogen that causes primary atypical pneumonia. M. pneumoniae motility and infectivity are mediated by the immunodominant proteins P1 and P40/P90, which form a transmembrane adhesion complex. Here we report the structure of P1, determined by X-ray crystallography and cryo-electron microscopy, and the X-ray structure of P40/P90. Contrary to what had been suggested, the binding site for sialic acid was found in P40/P90 and not in P1. Genetic and clinical variability concentrates on the N-terminal domain surfaces of P1 and P40/P90. Polyclonal antibodies generated against the mostly conserved C-terminal domain of P1 inhibited adhesion of M. pneumoniae , and serology assays with sera from infected patients were positive when tested against this C-terminal domain. P40/P90 also showed strong reactivity against human infected sera. The architectural elements determined for P1 and P40/P90 open new possibilities in vaccine development against M. pneumoniae infections. Adhesion of the human pathogen Mycoplasma pneumoniae to pulmonary epithelial cells is mediated by a transmembrane complex composed of proteins P1 and P40/P90. Here, the authors present the structures of M. pneumoniae P1 and P40/P90, show that P40/P90 binds sialylated oligosaccharides and have also determined the crystal structures of P40/P90 complexes with 3’-Sialyllactose and 6’-Sialyllactose, which provide insights into the mechanisms of adhesion and gliding on host cell surfaces.

ObjectivesAlthough rapid screening and treatment programmes have been recently implemented to tackle STIs, testing Mycoplasma genitalium (MG) among asymptomatic populations is not currently recommended due to the lack of scientific evidence and the emergence of antibiotic resistance. The main objective of this study was to estimate the prevalence of MG and macrolide resistance among asymptomatic people visiting a point of care service for rapid STI screening and to identify risk factors associated with the acquisition of this infection.MethodsBetween October 2017 and January 2018, a total of 890 asymptomatic individuals attending to the STI screening service Drassanes Exprés in Barcelona, Spain, were tested for MG and macrolide resistance using the molecular ResistancePlus MG assay (SpeeDx, Australia). Asymptomatically infected individuals were invited to attend the STI Unit for resistance-guided antimicrobial therapy.ResultsOverall, the prevalence of MG was 7.4% (66/890; 95% CI 5.8% to 9.3%), being higher among men who have sex with men (MSM) (46/489) compared with heterosexual men and women (20/401; p=0.012). Macrolide resistance was found in 32/46 (69.6%; 95% CI 54.2% to 82.3%) MSM, while only 2/20 (10.0%; 95% CI 1.2% to 31.7%) infections among heterosexuals presented macrolide resistance-mediated mutations (p<0.001). MSM behaviour, receptive anal intercourse, HIV positive status, syphilis history and high-risk sexual activity (more than five sexual partners in the last 3 months) were significantly associated with MG infection. Furthermore, the resistance-guided therapy approach was implemented in 36/66 (54.6%) individuals.ConclusionsThe research provides further data regarding the prevalence of MG and macrolide resistance among asymptomatic individuals. It also identifies higher risk subpopulations which might be targets for MG screening. Nevertheless, there is insufficient data to justify MG testing among asymptomatic individuals and current STI guidelines should be followed until evidence shows the cost and effectiveness of screening.

Background/Objectives: Nontuberculous mycobacteria (NTM) infections are rising, particularly those by Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MAB). Treating NTM infections is challenging due to their poor response to antibiotics. This study aimed to optimize the treatment of NTM infection by selecting antibiotics with bactericidal activity for combination therapy. To do this, we used the minimum bactericidal concentration (MBC) determination approach to define bactericidal or bacteriostatic activity. We developed three main objectives: validate a new method to determine MBC based on a reincubation method, determine MBC values of 229 NTM clinical isolates using the reincubation method, and evaluate antibiotic stability in preincubated microtiter plates. Methods: First, we assessed the stability of the antibiotics included in SLOWMYCOI Sensititre™ microtiter plates. Five strains of MAC were studied comparing the minimum inhibitory concentrations (MICs) of those preincubated for seven days vs. non-incubated plates. Then, we evaluated the percentage of reproducibility of MBC values using two methods, reincubation and subculturing (standard or traditional method) in 30 MAC isolates. Finally, we validated the reincubation method and prospectively determined the MBC values of the 229 NTM clinical strains. Results: Antibiotic stability: The MIC was equivalent after 7 and 14 days for all the antibiotics, except rifampicin, for which the MIC increased by 2- to 3-fold after preincubation. Reincubation method: The percentage of reproducibility of the MBC values between the two methods was 95.2% (range 76.6% to 100%). Prospective validation: MBC/MIC ratios revealed differential bactericidal activity for most antibiotics according to the different species, being bactericidal in M. avium and Mycobacterium xenopi, and predominantly bacteriostatic in MAB. Conclusions: Preincubation of Sensititre™ microtiter plates did not alter the MIC values of the antibiotics included except for rifampicin, suggesting a loss of activity. MBC determination can be easily performed by the Reincubation method presented. MBC values provide useful additional information regarding MIC values since the MBC/MIC ratio reveals whether antibiotics have bactericidal or bacteriostatic activity according to the species, which is pivotal for selecting the most adequate antibiotic combination to ensure efficient treatment management.

Purpose To evaluate the detection rate of septic metastases in catheter-related S. aureus bacteremia (CR-SAB) episodes by using [18F]FDG-PET/CT. Methods We conducted a retrospective, before-and-after, single-center study of a prospectively identified catheter-related SAB (CR-SAB) cohort at Hospital Clínic Barcelona. All adult patients hospitalized from January 2006 to December 2022 were included. Primary outcome was the detection of septic metastases before and after integrating [18F]FDG-PET/CT into the diagnostic workflow of CR-SAB in January 2020. Secondary outcomes included 30-day mortality, length of stay, and treatment duration. Results A total of 598 episodes of CR-SAB were included, 100 in the post-intervention period (2020–2022) and 498 in the pre-intervention period (2006–2019). [18F]FDG-PET/CT scan was performed in 28/100 episodes (28.0%) in post-intervention period, versus 9/498 in pre-intervention period (1.8%). Septic metastases detection rate was higher after [18F]FDG-PET/CT implementation (22/100, 22% vs. 56/498, 11.2% p .004), mainly due to pulmonary septic emboli (13/100, 13.0% vs . 12/498, 2.4% p  < .001) and osteoarticular seeding (7/100, 7.0% vs . 11/498, 2.2% p .019). Neither pulmonary septic emboli nor osteoarticular metastases increased 30-day mortality (3/25, 12.0% vs. 57/573, 10.0%, p .732; and 2/18, 11.1% vs. 58/580 10.0%, p .702, respectively). Patients with septic metastases had longer treatment [25.0 (16.0–37.0) vs . 15.0 (13.0–19.0) days, p  < .001]. Conclusions [18F]FDG-PET/CT use in patients with CR-SAB was associated with a higher rate of septic metastases diagnosis, mainly pulmonary and osteoarticular, resulting in longer treatment, but no differences in clinical outcomes were observed.

BackgroundSTIs are a major public health concern. Screening programmes for asymptomatic users are key components of STI control. Traditional limitations of screening programmes include low population coverage and delays in treatments, thus reducing the expected impact on STI control. In our centre, the normal time from test to results was 4 days, and 7 days until treatment was established.To reduce time to treatment and to increase population coverage, we developed ‘Drassanes Exprés’, a testing service for asymptomatic STIs. The objectives of this study were to provide a guide for the implementation of a service with these characteristics and to evaluate the results of this intervention.MethodsThe Drassanes Exprés programme was launched in Spain on 07 November 2016 as a public, confidential and free-of-charge testing service for asymptomatic STIs, with same-day result notification. For this walk-in service, confidentiality was obtained by registering all information into the Laboratory Internal Software instead of the Electronic Patient Records. Samples were processed in a point-of-care laboratory and result notification was provided via mail or short message service.Information about workflow, screening protocols and result interpretation is detailed. Additionally, demographic characteristics, STI prevalence, and time from patients’ sample collection to notification and treatment are analysed.ResultsBetween 07 November 2016 and 07 November 2019, 13 993 users attended the Drassanes Exprés screening programme. Of these, 0.5% were transgender people, 29.3% women, 45.2% men who have sex with men and 25.1% men who have sex with women. The median age was 31 years (range: 26–39 years). Overall, 14.6% of users tested positive for at least one STI. The most prevalent infection was Chlamydia trachomatis (8.3%), followed by Neisseria gonorrhoeae (5.7%), syphilis (1.8%), HIV (0.4%) and hepatitis C virus (0.2%). The median time from test to results was 2.4 hours (range: 2–3.1 hours). Of 2049 users diagnosed with an STI, treatment was achieved in 97.0% of cases; the average time to treatment was 2.0 days.ConclusionsDrassanes Exprés is the first public programme for rapid, asymptomatic, STI screening and treatment in Spain. Assessing high-risk practices and providing confidentiality, easy access and rapid results/treatments are key elements in the development of STI screening programmes.

Introduction: The incidence of pneumococcal disease (PD) in people living with HIV (PLWH) is higher than in the general population; therefore, this study aimed to analyze its incidence, clinical characteristics and vaccination coverage in PLWH. Methods: We conducted a retrospective, single-center study between 2015 and 2024 in Hospital Clínic, Barcelona, involving HIV patients who presented with PD during the study period (any patient with a microbiologically confirmed result). A descriptive analysis of cases was carried out and compared with patients who did not present PD during the study period. Results: A total of 177 episodes of PD were identified in 148 individuals, with a cumulative incidence of 1.7% (95% CI: 1.4–2.0). The median age at PD diagnosis was 45.9 (36–53) years; 64% of patients were Spanish-born; 50% of patients were men who have sex with men (MSM); the HIV transmission mode was intravenous drug use in 28% of cases; the median CD4 nadir was 181 (58–324) cells/mm3; the median CD4 prior to PD was 429 (240–663) cells/mm3; and the median peak HIV viral load (VL) was 176,839 (20,900–502,000) copies/mL. Intravenous drug use (OR 3.43; 95% CI 2.19–5.36; p < 0.001), peak HIV VL (OR 1.11; 95% CI 1.02–1.21; p = 0.011), and CD4 nadir (OR 0.92; 95% CI 0.87–0.98; p = 0.005) were independently associated with PD, and fifty-one percent of patients had not received any vaccination prior to their PD episode. Conclusion: PD incidence was high in our study and associated with poor immunological status. Research on new strategies to improve vaccination coverage and immunogenicity in PLWH is needed.

Immune imprinting or original antigenic sin (OAS) is the process by which the humoral memory response to an antigen can inhibit the response to new epitopes of that antigen originating from a second encounter with the pathogen. Given the situation of the COVID-19 pandemic, multiple vaccines have been developed against SARS-CoV-2 infection. These vaccines are directed to the spike protein (S protein) of the original variant of Wuhan D614G. Vaccine memory immune response against S protein in noninfected subjects could inhibit, through the OAS mechanism, the response to new epitopes of SARS-CoV-2 after infection. The present study analyzes whether the memory antibody B cell response generated by mRNA vaccines against S protein can inhibit the primary antibody immune response to other SARS-CoV-2 antigens, such as nucleocapsid protein (N protein). SARS-CoV-2 primary infection in vaccinated healthcare workers (HCWs) produced significantly lower titers of anti-N antibodies than that in nonvaccinated HCWs: 5.7 (IQR 2.3-15.2) versus 12.2 (IQR 4.2-32.0), respectively (p=0.005). Therefore, spike protein vaccine-induced immune imprinting (original antigenic sin) reduces N protein antibody response.